Pancreas
The pancreas is an elongated gland (exo- and endocrine) in the abdominal cavity, medial to the duodenum. It's primary function is the secretion of regulatory hormones and pancreatic juice for digestion. Gross Anatomy It can be divided into 3 sections: a body, a head, and a tail. The head is the most lateral part. It lies in the loop of the duodenum to which it is attached by connective tissue and with which it shares a common blood supply. The body and tail extend medially across the midline towards the hilum of the spleen. The pancreatic duct (duct of Wirsung), extends through the long axis of the gland to the duodenum and empties via the ampulla of Vater into the duodenum. This is the route pancreatic juice takes. Some people also have an accessory pancreatic duct. Bile also exits through the ampulla of Vater. The pancreas is composed of exocrine tissue (secretions exit through a duct onto an epithelium rather than directly into the bloodstream), and endocrine tissue (secretions go directly into the bloodstream). The exocrine tissue secretes pancreatic juice for digestion whereas the endocrine tissue secretes glucagon and insulin for metabolism regulation. Exocrine tissue The main secretion of exocrine tissue is pancreatic juice, which enters the duodenum via the pancreatic duct, which shares a common exit with the common bile duct. The sphincter of Oddi controls the entrance of pancreatic juice and bile into the duodenum; it is contracted between meals to seal the junction closed. The sphincter is relaxed by the action of cholecystokinin. Exocrine dysfunction may be a result of disorders of the pancreas or of the ducts and sphincter. For example, duct blockage may impair bile flow and cause jaundice. In the small intestine, the chyme from the stomach mixes with pancreatic juices, bile, and other secretions of the intestinal walls. The pancreatic juice provides most of the digestive enzymes and its high HCO3 content raises the pH to a level more suited to the enzyme's function. 'Anatomy' The exocrine units are tubuloacinar glands which resemble bunches of grapes. These units surrouns the endocrine units of the pancreas - the islets of Langerhans. A thin, loose-fitting layer of connective tissue surrounds the gland. Septa extend from here into the gland to divide it into lobules. More prominent areas of connective tissue surround the main ducts, blood vessels, and nerves that penetrate the gland. Small mucous glands in the surrounding connective tissue secrete mucus into the ducts. 'Histology' The exocrine units (or 'pancreatons') of the pancreas consist of a duct and a terminal acinar portion. The duct is called an intercalated duct. This duct drains into a larger intralobular duct, which then drains into an extralobular duct, ever larger ducts, and finally, a main collecting duct called the pancreatic duct. The acinus is a rounded, hollow structure made up of several, mainly pyramidal epithelial cells. They secrete the digestive enzymes of the pancreatic juice. The polarisation of the cells is evident; the nucleus and rough endoplasmic reticulum are close to the basilar layer, whilst the Golgi apparatus and zymogen (enzyme precursor), granules are more towards the apical layer. Mitochondria are littered throughout the cell and are smaller than normal. Staining with haemotoxylin or basic dyes will highlight the RER as this is the site of digestive enzyme production, whilst acidic dyes will highlight the golgi and enzymes (basilar and apical portions respectively). Microvilli extend from the apical surface of the acinar cells into the lumen. The tight junctions between neighbouring acini are called zonulae adherens; they seperate the fluid in the intercellular spaces from that in the lumen and are impermeabe to large macromolecules (i.e. digestive enzymes), but allow water and ion exchange. Any problems with these tight junctions may be a contributory cause to pancreatitis. Gap junctions allow for rapid membrane potential changes to be transmitted and for the exchange of low molecular weight molecules (<1400kDa) between cells. The intercalated ducts begin inside the acinus (a feature unique to secretory glands). The duct cells in the acinus are called centroacinar cells. They stain lightly with eosin. They are squamous with a nucleus placed centrally, and are continuous with the duct cells outsite of the acinus, although these cells are more flattened. Duct cells are joined by tight junctions to prevent large molecules from entering interstitial space. They also have gap junctions to permit the transmission of membrane potential changes between cells. These ducts lead to the intralobular ducts which are lined with cuboidal or low columnar epithelium. Larger ducts contrain interlobular connective tissue cells and APUD cells. 'Pancreatic juice' Pacreatic juice entering the duodenum is a mixture of enzymes and alkaline substances. If ducts near the acini are ligated or blocked scarcely affects the alkaline secretions, but markedly reduces the release of enzymes (indicating enzymes are secreted by acinar cells, whilst the alkaline secretions come from the duct cells). The alkaline secretions come largely from the centroacinar cells, and the cells of the intralobular and interlobular ducts. 'Alkaline secretions' 'Functions' The smaller or 'upper' ducts secrete an isotonic juice rich in bicarbonate but containing only trace amounts of enzymes. There is a continuous resting secretion level, but during a meal this can elevate to 14 times the resting rate. It contains Na+, K+, HCO3-, Mg2+, Ca2+, Cl-, and other ions present in concetrations similar to plasma. It has a high pH due to its prominent HCO3- content. Pancreatic juice is secreted into the duodenum where it mixes with and neutralises the highly acidic chyme from the stomach. This process: *Provides the higher pH that the pancreatic enzymes need to function, *Allows for micelle formation, an important step in fat absoprtion, *Protects the intestinal mucosa against damage and ulceration from the stomach acid. 'Secretion mechanism' The initial step in the secretion of HCO3- from the centroacinar and upper duct cells involves CO2 reacting with water. H+ ions are released from the cell and into the blood, where they react with serum HCO3- to produce CO2 and water. Some of this CO2 diffuses into the cell, where it reacts with intracellular water to generate carbonic acid (H2CO3), a reaction catalysed by carbonic anhydrase II. The carbonic acid dissociates, forming HCO3- and H+ ions, which are released into the blood to restart the cycle. The downhill CO2 gradient between the blood and the cell is maintained because the intracellular CO2 is constantly being used up, encouraging the diffusion of more CO2 into the cell from the blood. The HCO3- ions are secreted through the luminal membrane of the centroacinar and upper duct cells via a Cl-/HCO3- exchange protein. The H+ ions are secreted into the blood (hence pancreatic blood is temporarily acidic, especially following a meal as HCO3- production rises). The H+ rise is also important in combatting the alkaline tide produced during a meal by the secreting stomach. 'Pancreatic enzymes' Endocrine tissue In addition to digestive juices, the pancreas also secretes two regulatory hormones, important in the control of blood-glucose levels, and lipid and protein metabolism; glucagon and insulin. It also secretes amylin, somatostatin, and pancreatic polypeptide, though they are produced in much smaller amounts and have less effect on the body. The endocrine tissue is composed of at least five kinds of cells, all of which are contained in around 1-2million small (~0.3mm diameter) clusters called islets of Langerhans. A thin fibrous connective tissue separates them from the rest of the pancreas: *Alpha cells (15-20% of cells) produce glucagon *Beta cells (65-80% of cells) produce insulin and amylin *Delta cells (3-10% of cells) produce somatostatin *Gamma cells (3-5% of cells) produce pancreatic polypeptide *Epsilon cells (<1% of cells) produce ghrelin *Insulin: activates beta cells and inhibits alpha cells *Glucagon: activates alpha cells which activates beta cells and delta cells *Somatostatin: inhibits alpha cells and beta cells